With the growth of biological information, the efficiency of database retrieval has become central to the biological enterprise. In particular, one can change a retrieval method and must be able to evaluate whether the change is an improvement or not. We are developing methods based on the statistical bootstrap to assign statistical significance to improvements in database retrieval. The methods are based on mathematical central limit theorems describing the behavior of the receiver operating characteristic curve [n] under bootstrapping. In particular, our methodology has already been applied to determine which changes to the PSI-BLAST program actually constitute improvements.